Microhydration effects on the electronic spectra of protonated polycyclic aromatic hydrocarbons: [naphthalene-(H2O)(n = 1,2)]H+

Vibrational and electronic spectra of protonated naphthalene (NaphH(+)) microsolvated by one and two water molecules were obtained by photofragmentation spectroscopy. The IR spectrum of the monohydrated species is consistent with a structure with the proton located on the aromatic molecule, NaphH(+)-H(2)O. Similar to isolated NaphH(+), the first electronic transition of NaphH(+)-H(2)O (S(1)) occurs in the visible range near 500 nm. The doubly hydrated species lacks any absorption in the visible range (420-600 nm) but absorbs in the UV range, similar to neutral Naph. This observation is consistent with a structure, in which the proton is located on the water moiety, Naph-(H(2)O)(2)H(+). Ab initio calculations for [Naph-(H(2)O)(n)]H(+) confirm that the excess proton transfers from Naph to the solvent cluster upon attachment of the second water molecule.     

DNA-templated preparation of gold nanoparticles

DNA-mediated gold nanoparticles were prepared by chemical reduction of DNA-Au(III) complex. The DNA-Au(III) was first formed by reacting DNA with HAuCl? at a pH of 5.6. The complex in solution was reacted with hydrazine reducing Au(III) to Au. The reduced Au formed nanodimensional aggregates. The particle distributions were obtained by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). This method resulted in a rather uniform dispersion of Au nanoparticles of near-spherical shape and 45~80 nm in diameter. Gold nanoparticles were embedded and stabilized by DNA.     

Progressive formation of fine and coarse ripples on SiC surface by repeated irradiation of femtosecond laser pulses

In this work, we report the progressive formation of first nanoparticles, next fine ripples, and eventually coarse ripples during the irradiation of single-crystal 6H-SiC surfaces with increasing number of femtosecond laser pulses (λ = 515 nm, τ = 250 fs, repetition rate = 100 kHz). At laser fluences greater than the single-pulse ablation threshold, nanoparticles were produced on the surface by the first few pulses over which fine ripple patterns overlapped at increased pulse numbers. As the pulse number was further increased over ten, the surface was gradually transformed into a coarse ripple–covered one. At laser fluence below the threshold, however, only fine ripples were formed nonuniformly.     

An Fc variant with two mutations confers prolonged serum half-life and enhanced effector functions on IgG antibodies

The pH-selective interaction between the immunoglobulin G (IgG) fragment crystallizable region (Fc region) and the neonatal Fc receptor (FcRn) is critical for prolonging the circulating half-lives of IgG molecules through intracellular trafficking and recycling. By using directed evolution, we successfully identified Fc mutations that improve the pH-dependent binding of human FcRn and prolong the serum persistence of a model IgG antibody and an Fc-fusion protein. Strikingly, trastuzumab-PFc29 and aflibercept-PFc29, a model therapeutic IgG antibody and an Fc-fusion protein, respectively, when combined with our engineered Fc (Q311R/M428L), both exhibited significantly higher serum half-lives in human FcRn transgenic mice than their counterparts with wild-type Fc. Moreover, in a cynomolgus monkey model, trastuzumab-PFc29 displayed a superior pharmacokinetic profile to that of both trastuzumab-YTE and trastuzumab-LS, which contain the well-validated serum half-life extension Fcs YTE (M252Y/S254T/T256E) and LS (M428L/N434S), respectively. Furthermore, the introduction of two identified mutations of PFc29 (Q311R/M428L) into the model antibodies enhanced both complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity activity, which are triggered by the association between IgG Fc and Fc binding ligands and are critical for clearing cancer cells. In addition, the effector functions could be turned off by combining the two mutations of PFc29 with effector function-silencing mutations, but the antibodies maintained their excellent pH-dependent human FcRn binding profile. We expect our Fc variants to be an excellent tool for enhancing the pharmacokinetic profiles and potencies of various therapeutic antibodies and Fc-fusion proteins.Subject terms: Antibody therapy, Molecularly targeted therapy, Drug development     

Expression, purification, crystallization, and preliminary X-ray crystallographic analysis of OXA-17, an extended-spectrum β-lactamase conferring severe antibiotic resistance

OXA-17, an extended-spectrum β-lactamase (ESBL) conferring severe antibiotic resistance, hydrolytically inactivates β-lactam antibiotics, inducing a lack of eradication of pathogenic bacteria by oxyimino β-lactams and not helping hospital infection control. Thus, the enzyme is a potential target for developing antimicrobial agents against pathogens producing ESBLs. OXA-17 was purified and crystallized at 298 K. X-ray diffraction data from OXA-17 crystal have been collected to 1.85 Å resolution using synchrotron radiation. The crystal of OXA-17 belongs to space group P2₁2₁2₁, with unit-cell parameters a = 48.37, b = 101.12, and c = 126.07 Å. Analysis of the packing density shows that the asymmetric unit probably contains two molecules with a solvent content of 54.6%.     

Bis­[(2,2‐di­methyl‐1,3‐propane­diamine‐κ2N,N′)(piperidine‐2‐car­boxylato‐κ2N,O)­platinum(II)] sulfate

The title compound, [Pt(C₆H₁₀NO₂)(C₅H₁₄N₂)]₂(SO₄), crystallizes with two cations in the asymmetric unit. The two complex cations, which have a square‐planar Pt^II coordination, are chemically identical but differ slightly in the conformations of their amine groups. A neutral complex, viz. (2,2‐di­methyl‐1,3‐propane­di­amine‐κ²N,N′)bis(2‐piperidine­carb­oxyl­ato‐κN)platinum(II), is shown to form in solution and to change rapidly into the title compound.     

A linear program for the two-hub location problem

This paper considers the discrete two-hub location problem. We need to choose two hubs from a set of nodes. The remaining nodes are to be connected to one of the two hubs which act as switching points for internodal flows. A configuration which minimizes the total flow cost needs to be found. We show that the problem can be solved in polynomial time when the hub locations are fixed. Since there are at most ways to choose the hub locations, the two-hub location problem can be solved in polynomial time. We transform the quadratic 0–1 integer program of the single allocation problem in the fixed two-hub system into a linear program and show that all extreme points of the polytope defined by the LP are integral. Also, the problem can be transformed into a minimum cut problem which can be solved efficiently by any polynomial time algorithm.     

Local acid environment in poly(ethylene‐ran‐methacrylic acid) ionomers

The local environment of unneutralized carboxylic acid groups in poly(ethylene‐ran‐methacrylic acid) (E/MAA) ionomers neutralized with monovalent (Li and Na) and divalent (Ca and Zn) ions has been investigated with Fourier transform infrared spectroscopy. These unneutralized acid groups interact with one another to form acid dimers, and they associate with existing neutralized complexes. At room temperature, no free acids can be detected for any system, not even for pure E/MAA. With the acid dimer peak (1700 cm^?1) and a known unneutralized acid concentration, the concentration of acids associated with a neutralized complex can be determined. This concentration of associated acids increases with increasing neutralization, reaches a maximum below 50% neutralization, and then decreases toward zero near 80% neutralization. This behavior is perhaps due to the increased driving force for aggregation of the neutralization acids. Although Li, Na, and Ca contain similar concentrations of associated acids over the range of neutralizations, the Zn system contains far fewer associated acids (i.e., more acid dimers) at any particular neutralization level. These results are confirmed by an analysis of the absorbance in the neutralized region (1650–1500 cm^?1). © 2002 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 2833–2841, 2002     

Pricing under quality of service uncertainty: Market segmentation via statistical QoS guarantees

This article examines how performance-contingent pricing schemes with long-term statistical performance guarantees can be applied to many IT services. We study two forms of performance-contingent pricing, with rebate proportional to failure rate and fixed rebate for below-threshold performance. We show that threshold-performance contingency pricing can increase both profits and fairness (customers who receive higher benefits pay higher effective price) relative to standard pricing. But an even better solution is to offer a menu of performance guarantees: this can increase the firm’s profit and segment the market. Only service providers whose performance level is sufficiently better than the industry standard can benefit from this pricing mechanism.